Several tn homozygous mouse embryos are being studied so that the cause of lethality of the alleles at the T-locus can be determined. Two preimplantation lethal homozygotes (tw32 and t12) and an implantation lethal homozygote (t6) are being investigated. Common ultrastructural characteristics, i.e. binucleate cells, and excessive lipid, together with direct evidence of reduced energy metabolism prior to developmental arrest in all three mutants, suggest that the lethal effect of the various alleles is related to the defective intermediary metabolism. This defect results in reduced ATP synthesis at the developmental stage prior to death. Excessive lipid droplets and binucleate cells are found concomitantly with the depressed ATP synthesis. Prior to the stage at which the mutants show a reduced rate of ATP synthesis, these same embryos synthesize greater amounts at ATP than their wild-type counterparts. We believe that this results in a shunt at the level of Acetyl CoA into lipid production. Our research is designed to determine the level of the metabolic error in ATP synthesis and also if the excessive lipid is directly related to the depressed intermediary metabolism. The methods used in determining the level of action of the tn alleles will include ultrastructural, autoradiographic and biochemical techniques.